In vivo occupancy of striatal and temporal cortical D2/D3 dopamine receptors by typical antipsychotic drugs -: [123I]-epidepride single photon emission tomography (SPET) study

Background The dopamine hypothesis proposes that antipsychotic drugs act primarily through limbic cortical D-2/D-2-like dopamine receptor blockade. Aim To evaluate this hypothesis with the D-2/D-3-selective SPET probe [I-123]-epidepride. Method [I-123]-epidepride SPET scans were performed on 12 patients with schizophrenia treated with antipsychotics and 11 age- matched healthy controls. [I-123]-epidepride 'specific binding' to D-2/D-3 dopamine receptors was estimated, and relative percentage D-2/D-3 receptor occupancy by typical antipsychotic drugs determined. Results Mean (s.d.) daily dose was 669.12 (516.8) mg chlorpromazine equivalents. Mean percentage D-2/D-3, receptor occupancy was 81.6 (8.1) and 73.2 (13.9) in the temporal cortex and striatum respectively. Conclusions Typical antipsychotic drug treatment is associated with substantial temporal cortical D-2/D-3 receptor occupancy. The relationship between this and efficacy is poor in patients with treatment-resistant schizophrenia. Declaration of interest L.P. was supported by a Medical Research Council Clinician Scientist Fellowship. V.B. was supported by a research grant from Eli Lilly Pharmaceuticals.